Carboxylic acid to amide hydrogen bonding. 10-Oxo-semirubins

Using their amide (and pyrrole) groups, dipyrrinones act as hydrogen bonding receptors for carboxylic acids, as found in a large number of 10-oxo-semirubins (1-6). The latter can be synthesized readily by Friedel-Crafts coupling of 9-H dipyrrinones with half-ester acid chlorides or diacid dichlorides of α,ω-dicarboxylic acids, ranging from C₂ to C₁₀. With ω-oxo-alkanoic acid chains of C₅ or ≥C₅, intramolecular hydrogen bonding is observed. With acid chains <C₅ hydrogen bonding is not observed. Uncharacteristically (for dipyrrinones), 10-oxo-dipyrrinone acids (1-6) and their corresponding esters (1e-6e) remain monomeric in hydrogen bond promoting solvents.     

Highly sensitive luminescent metal-complex receptors for anions through charge-assisted amide hydrogen bonding

Two structurally simple and easily synthesized luminescent anion receptors featured with an amide-type anion binding site and rhenium(I) tricarbonyl pyridine signaling units have been developed, and they display outstanding sensitivity and selectivity toward a variety of anionic species. These complexes are highly emissive in solution. Upon anion binding, the emission intensity was significantly quenched. The sensitivities of these complexes are so high that the emission intensity can be effectively quenched by as much as 10% even in the presence of only 10(-8) M cyanide or fluoride anions. The ability of formation of intramolecular hydrogen bonding between the amide protons and central pyridine is believed to be responsible for the observed high selectivity.     

Supramolecular amide and thioamide synthons in hydrogen bonding patterns of N-aryl-furamides and N-aryl-thiofuramides

The supramolecular synthon of amide group in the primary and secondary amides is well recognized to be infinite chains of the C(4) type formed by the intermolecular hydrogen bond of the type N–HO=C. On the other hand, there is a lack of structural data for the thioamides. Three compounds belonging to the class of N-aryl-fura-mides (N-(4-bromophenyl)-5-bromo-2-furancarboxamide, N-(4-chlorophenyl)-5-bromo-2-furancarboxamide) and to the class of N-aryl-thiofuramide (N-(4-methoxyphenyl)-2-furanthiocarboxamide) are prepared and characterized by the NMR spectroscopy in solution; molecular and crystal structures in the solid state have been determined by X-ray single crystal diffractometry and the structures in the gas phase by DFT and AM1 calculations. The investigation is carried out in order to establish supramolecular amide and thioamide synthons of hydrogen bonding patterns in these crystal structures. The geometry of the N–HO=C and the N–HS=C type of hydrogen bonds are compared due to the possibility of the N–H amide group to form intramolecular hydrogen bond with the furan oxygen atom, thus, commonly, leading to the three-center hydrogen bond pattern. The competition between the S=C proton acceptor of thioamides and the other proton acceptors (such as methoxy group) for the amide N–H proton donor group has been investigated. In that context, the above-mentioned compounds are correlated with the others of this class, structurally determined, so far.     

Cooperative hydrogen bonding effects are key determinants of backbone amide proton chemical shifts in proteins

A computational methodology for backbone amide proton chemical shift (delta(H)) predictions based on ab initio quantum mechanical treatment of part of the protein is presented. The method is used to predict and interpret 13 delta(H) values in protein G and ubiquitin. The predicted amide-amide delta(H) values are within 0.6 ppm of experiment, with a root-mean-square deviation (RMSD) of 0.3 ppm. We show that while the hydrogen bond geometry is the most important delta(H)-determinant, longer-range cooperative effects of extended hydrogen networks make significant contributions to delta(H). We present a simple model that accurately relates the protein structure to delta(H).     

Dependence of glycine CH2 stretching frequencies on conformation, ionization state, and hydrogen bonding

We experimentally and theoretically examined the conformation, pH, and temperature dependence of the CH2 stretching frequencies of glycine (gly) in solution and in the crystalline state. To separate the effects of the amine and carboxyl groups on the CH2 stretching frequencies we examined the Raman spectra of 2,2,2-d3-ethylamine (CD3-CH2-NH2) and 3,3,3-d3-propionic acid (CD3-CH2-COOH) in D2O. The symmetric (nusCH2) and asymmetric (nuasCH2) stretching frequencies show a significant dependence on gly conformation. We quantified the relation between the frequency splitting (Delta = nuasCH2-nusCH2) and the xi angle which determines the gly conformational geometry. This relation allows us to determine the conformation of gly directly from the Raman spectral frequencies. We observe a large dependence of the nusCH2 and nuasCH2 frequencies on the ionization state of the amine group, which we demonstrate theoretically results from a negative hyperconjugation between the nitrogen lone pair and the C-H antibonding orbitals. The magnitude of this effect is maximized for C-H bonds trans to the nitrogen lone pair. In contrast, a small dependence of the CH2 stretching frequencies on the carboxyl group ionization state arises from delocalization of electron density from carboxyl oxygen to C-H bonding orbitals. According to our experimental observations and theoretical calculations the temperature dependence of the nusCH2 and nuasCH2 of gly is due to the change in the hydrogen-bonding strength of the amine/carboxyl groups to water.     

Investigating the effect of hydrogen bonding environments in amide cleavage reactions at zinc(II) complexes with intramolecular amide oxygen co-ordination

Amide oxygen co-ordination to a zinc(II) ion around a hydrogen bonding microenvironment is a common structural/functional feature of metalloproteases. We report two strategies to position hydrogen bonding groups in the proximity of a zinc(II)-bound amide oxygen, and we investigate their effect on the stability of the amide group. Polydentate tripodal ligands (6-R1-2-pyridylmethyl)-R2 (R1= NHCOtBu, R2= N(CH2-py-6-X)2 X = H L1, X = NH2, H L2, X = NH2 L3) form [(L)Zn]2+ cations (L =L1, 1; L2, 2; L3, 3) with intramolecular amide oxygen co-ordination (1-3), and intramolecular N-H...O=C(amide) hydrogen bonding (2, 3) rigidly fixed by the ligand framework. 1-3 undergo cleavage of the tert-butyl amide upon addition of Me4NOH.5H2O (1 equiv.) in methanol at 50(1) degrees C. Under these conditions the half-life, t(1/2), of the amide bond is 0.4 h for 1, 9 h for 2 and 320 h for 3. Mononuclear zinc(II) complexes of (6-NHCOtBu-2-pyridylmethyl)-R2(R2= N(CH2CH2)2S) L4 and chelating N2 ligands without hydrogen bonding groups (1,10-phenanthroline L5, 2-(aminomethyl)pyridine L6) as control compounds, and with an amino hydrogen bonding group (6-amino-2-(aminomethyl)pyridine L7) have been synthesised. Amide cleavage is in this case faster at the zinc(II) complex with the amino hydrogen bonding group. Thus, hydrogen bonding environments can both accelerate and slow down amide bond cleavage reactions at zinc(II) sites. Importantly, the magnitude of the effect exerted by the hydrogen bonding environments was found to be significant; 800-fold rate difference. This result highlights the importance of hydrogen bonding environments around metal centres in amide cleavage reactions, which may be relevant to the chemistry of natural metalloproteases and applicable to the design of more efficient artificial protein cleaving agents.     

Dependence of (35)Cl NQR on hydrogen bonding and temperature in dichlorophenol-aniline charge transfer complexes

The hydrogen-bonded charge transfer complexes of aniline with pi-acceptors (or proton donors) such as 2,5-, 2,6-, 3,4- and 3,5-dichlorophenol were prepared. The (35)Cl nuclear quadrupole resonance (NQR) frequencies of these charge transfer complexes in the temperature range 77-300 K were measured to ascertain the existence or otherwise of a phase transition upon complex formation. Further, the NQR frequency and asymmetry parameter of the electric field gradient at the site of quadrupole nucleus were used to estimate the chemical bond parameters, namely ionic bond, double bond character of the carbon-chlorine(C--Cl) bond and the percentage charge transfer between the donor-acceptor components in charge transfer complexes. The effect of hydrogen bonding and temperature on the charge transfer process is analysed.     

Photocycloaddition of four-carbon-tethered pyridones. Intramolecular hydrogen bonding and facilitated amide hydrolysis by a proximal secondary alcohol

Four-carbon-tethered pyridones undergo photocycloaddition to give exclusively trans-[4 + 4] products. The presence of a tether alcohol engenders a solvent-dependent diastereoselectivity for the cycloaddition by intramolecular hydrogen bonding to the adjacent pyridone. Following cycloaddition, the alcohol can deliver a carbonyl group to the proximal, hindered amide nitrogen, leading to a very facile amide hydrolysis.     

Positive homotropic allosteric binding of benzenediols in a hydrindacene-based exoditopic receptor: cooperativity in amide hydrogen bonding

The preparation and complexation properties of a hydrindacene-based exoditopic receptor, that exhibits a positive homotropic allosteric binding process toward benzenediols, are described. The exoditopic receptors form 1:2 complexes with resorcinols, catechol, and 3-hydroxybenzyl alcohol with K2/K1 = 3-33. Both the entropy and the enthalpy terms are important in this allosteric system; the crystallographic studies provide the first clear evidence that the cooperativity in amide hydrogen bonding by polarization contributes to the positive homotropic allosteric binding property.     

The vibrations of hydrogen bonds

I present recent inelastic incoherent neutron scattering (INS) work involving the study of the H-bond vibrations. These vibrations have spectral consequences which are strongly dependent upon spectroscopic technique, and these will be indicated for IR and Raman, and detailed for INS. The vibrational dynamics of the simple FHF⁻ will be used by way of an example. These INS results demonstrate that the latest generation of neutron spectrometers provides new insights into H-bonding dynamics.     

On differences between hydrogen bonding and improper blue-shifting hydrogen bonding.

Twenty two hydrogen-bonded and improper blue-shifting hydrogen-bonded complexes were studied by means of the HF, MP2 and B3LYP methods using the 6-31G(d,p) and 6--311 ++G(d,p) basis sets. In contrast to the standard H bonding, the origin of the improper blue-shifting H bonding is still not fully understood. Contrary to a frequently presented idea, the electric field of the proton acceptor cannot solely explain the different behavior of the H-bonded and improper blue-shifting H-bonded complexes. Compression of the hydrogen bond due to different attractive forces-dispersion or electrostatics--makes an important contribution as well. The symmetry-adapted perturbation theory (SAPT) has been utilized to decompose the total interaction energy into physically meaningful contributions. In the red-shifting complexes, the induction energy is mostly larger than the dispersion energy while, in the case of blue-shifting complexes, the situation is opposite. Dispersion as an attractive force increases the blue shift in the blue-shifting complexes as it compresses the H bond and, therefore, it increases the Pauli repulsion. On the other hand, dispersion in the red-shifting complexes increases their red shift.     

Effect of hydrogen bonding on the frequency of the out-of-plane deformation vibrations of the NH bonds in pyrazole and imidazole molecules

The assignment of the frequency of the out-of-plane deformation vibration of pyrazole on the basis of an investigation of the temperature dependence of the IR spectrum is reexamined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1388–1389, October, 1974.     

Effects of electrospray capillary temperature on amide hydrogen exchange

Amide hydrogen/deuterium (H/D) exchange coupled with proteolysis, high-perfeomance liquid chromatographic (HPLC) separation and mass spectrometry (MS) has become a powerful tool to study protein dynamics in solution. Prior to the execution of H/D exchange experiments, various experimental parameters have to be set, including proteolysis, HPLC, and MS conditions. Here we investigate the effects of electrospray capillary temperature on deuterium retention in backbone amides of various pepsin-generated cytochrome c peptides. Lower capillary temperature generally helps retain more deuterium than higher capillary temperature. When the capillary temperature was 150 degrees C, on average 26% more deuterium was retained than when the capillary temperature was set at 250 degrees C. The effects of capillary temperature varied depending on the ions monitored. There was little difference in deuterium retention among different charge state species of the same peptide at 150 degrees C. However, a lower charge state ion loses more deuterium atoms going from 150 degrees C to 250 degrees C than the corresponding higher charge state species. These results indicate that the capillary temperature should be optimized not only to maximize the signal-to-noise of each ion followed in H/D exchange experiments, but also to minimize the deuterium loss of the ions. Also the loss of deuterium in several ions, especially lower charge state ones, should be monitored in the optimization, as the temperature effects vary among ions and are more significant for lower charge state ions.     

Hydrogen bonding of carboxyl and amide groups to nucleosides

Carboxylic acid-nucleoside systems are studied by infrared spectroscopy. Intermolecular interactions of these systems in aqueous solution are investigated as a function of the degree of hydration and ΔpK_a. On the other hand, thermodynamic parameters for the association of N-methyl-acetamide with lactams in organic solvents have been determined by infrared spectroscopy. The low enthalpy values suggest open dimers formation.     

New supramolecular architectures based on hydrogen bonding

Heterocyclic compounds containing two and three adjacent hydrogen bond donor and acceptor sites in all possible arrangements were synthesized (see generalized structures shown below) to study and use their “base-pairing” capabilities. With two adjacent donor and acceptor groups there are three possible arrangements and these form two types of complexes (DA·AD and AA·DD). Three adjacent hydrogen bond donor and acceptor sites can be arranged in six different ways and these form three different complexes (ADA·DAD, AAD·DDA, and AAA·DDD).